Left Ventricular Unloading Increases the Coronary Collateral Flow Index Before Reperfusion and Reduces Infarct Size in a Swine Model of Acute Myocardial Infarction.

Background Unloading the left ventricle and delaying reperfusion reduces infarct size in preclinical models of acute myocardial infarction. We hypothesized that a potential explanation for this effect is that left ventricular (LV) unloading before reperfusion increases collateral blood flow to ischemic myocardium. Methods and Results Acute myocardial infarction was induced by balloon occlusion of the left anterior descending artery for 120 minutes in adult swine, followed by reperfusion for 180 minutes. After 90 minutes of occlusion, animals were assigned to 30 minutes of continued occlusion (n=6) or to 30 minutes of support with either an Impella CP (n=4) or venoarterial extracorporeal membrane oxygenation (n=5) with persistent occlusion. The primary end point was measures of microcirculatory blood flow including the collateral flow index (CFI) during left anterior descending artery occlusion as (Pw-RA)/(Pa-RA), where Pa, Pw, and RA are aortic, coronary wedge, and right atrial pressure, respectively. Infarct size was quantified using triphenyltetrazolium chloride. Compared with continued occlusion, Impella, not venoarterial extracorporeal membrane oxygenation, reduced infarct size relative to the area at risk. Before reperfusion, Impella reduced LV stroke work by 25% and increased the CFI by 75%, but venoarterial extracorporeal membrane oxygenation did not. Among all groups, the change in CFI between 90 and 120 minutes correlated inversely with the change in LV stroke work (r2=0.44, P=0.01) and infarct size (r2=0.41, P=0.02). Conclusions We report for the first time that 30 minutes of LV unloading during coronary occlusion increases the CFI, which correlates inversely with LV stroke work and infarct size. Venoarterial extracorporeal membrane oxygenation failed to increase the CFI and did not reduce infarct size.

Increased Plasma-Free Hemoglobin Levels Identify Hemolysis in Patients With Cardiogenic Shock and a Trans valvular Micro-Axial Flow Pump.

Hemolysis is a potential limitation of percutaneously delivered left-sided mechanical circulatory support pumps, including trans valvular micro-axial flow pumps (TVP). Hemolytic biomarkers among durable left ventricular assist devices include lactate dehydrogenase (LDH) >2.5 times the upper limit of normal (ULN) and plasma-free hemoglobin (pf-Hb) >20 mg/dL. We examined the predictive value of these markers among patients with cardiogenic shock (CS) receiving a TVP. We retrospectively studied records of 116 consecutive patients receiving an Impella TVP at our institution between 2012 and 2017 for CS. Twenty-three met inclusion/exclusion criteria, and had sufficient pf-Hb data for analysis. Area under receiver-operator characteristic (ROC) curve for diagnosing hemolysis were calculated. Mean age was 62 ± 14 years and ejection fraction was 15 ± 5%. Mean duration of support was 5.4 ± 3.5 days. Pre-device LDH levels were >2.5x ULN in 71% (n = 5/7) of 5.0 and 29% of CP patients, while pre-device pf-Hb levels were >20 mg/dL in 14% (n = 1/7) of 5.0 and 25% (n = 4/16) of CP patients. Given elevated baseline LDH and pf-Hb levels, we defined hemolysis as a pf-Hb level >40 mg/dL within 72 h post-implant plus clinical evidence of device-related hemolysis. We identified that 30% (n = 7/23) had device-related hemolysis. Using ROC curve-derived cut-points, an increase in delta pf-Hb by >27mg/dL, not delta LDH, within 24 h after TVP implant (delta pf-Hb: C-statistic = 0.79, sensitivity: 57%, specificity: 93%, p <0.05) was highly predictive of hemolysis. In conclusion, we identified a change in pf-Hb, not LDH, levels is highly sensitive and specific for hemolysis in patients treated with a TVP for CS.

Left Ventricular Unloading Before Reperfusion Promotes Functional Recovery After Acute Myocardial Infarction.

BACKGROUND: Heart failure after an acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a transvalvular axial-flow pump in the left ventricle and delaying myocardial reperfusion, known as primary unloading, limits infarct size after AMI. The mechanisms underlying the cardioprotective benefit of primary unloading and whether the acute decrease in infarct size results in a durable reduction in LV scar and improves cardiac function remain unknown. OBJECTIVES: This study tested the importance of LV unloading before reperfusion, explored cardioprotective mechanisms, and determined the late-term impact of primary unloading on myocardial function. METHODS: Adult male swine were subjected to primary reperfusion or primary unloading after 90 min of percutaneous left anterior descending artery occlusion. RESULTS: Compared with primary reperfusion, 30 min of LV unloading was necessary and sufficient before reperfusion to limit infarct size 28 days after AMI. Compared with primary reperfusion, primary unloading increased expression of genes associated with cellular respiration and mitochondrial integrity within the infarct zone. Primary unloading for 30 min further reduced activity levels of proteases known to degrade the cardioprotective cytokine, stromal-derived factor (SDF)-1α, thereby increasing SDF-1α signaling via reperfusion injury salvage kinases, which limits apoptosis within the infarct zone. Inhibiting SDF-1α activity attenuated the cardioprotective effect of primary unloading. Twenty-eight days after AMI, primary unloading reduced LV scar size, improved cardiac function, and limited expression of biomarkers associated with heart failure and maladaptive remodeling. CONCLUSIONS: The authors report for the first time that first mechanically reducing LV work before coronary reperfusion with a transvalvular pump is necessary and sufficient to reduce infarct size and to activate a cardioprotective program that includes enhanced SDF-1α activity. Primary unloading further improved LV scar size and cardiac function 28 days after AMI.

The role of acute circulatory support in ST-segment elevation myocardial infarction complicated by cardiogenic shock.

In the setting of ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock, three primary treatment objectives include providing circulatory support, ventricular unloading, and restoring myocardial perfusion. In addition to primary percutaneous coronary intervention, each of these three objectives can be achieved with appropriate use of an acute mechanical circulatory support (AMCS) pump. Over the past decade, utilization of percutaneously-delivered AMCS devices including the Impella axial-flow catheter, TandemHeart left atrial-to-femoral artery bypass system, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has grown exponentially. In this review, we will discuss the hemodynamic impact of each AMCS device and clinical data surrounding their use in the setting of STEMI complicated by cardiogenic shock.

Acute Biventricular Mechanical Circulatory Support for Cardiogenic Shock.

BACKGROUND: Biventricular failure is associated with high in-hospital mortality. Limited data regarding the efficacy of biventricular Impella axial flow catheters (BiPella) support for biventricular failure exist. The aim of this study was to explore the clinical utility of percutaneously delivered BiPella as a novel acute mechanical support strategy for patients with cardiogenic shock complicated by biventricular failure. METHODS AND RESULTS: We retrospectively analyzed data from 20 patients receiving BiPella for biventricular failure from 5 tertiary-care hospitals in the United States. Left ventricular support was achieved with an Impella 5.0 (n=8), Impella CP (n=11), or Impella 2.5 (n=1). All patients received the Impella RP for right ventricular (RV) support. BiPella use was recorded in the setting of acute myocardial infarction (n=11), advanced heart failure (n=7), and myocarditis (n=2). Mean flows achieved were 3.4±1.2 and 3.5±0.5 for left ventricular and RV devices, respectively. Total in-hospital mortality was 50%. No intraprocedural mortality was observed. Major complications included limb ischemia (n=1), hemolysis (n=6), and Thrombolysis in Myocardial Infarction major bleeding (n=7). Compared with nonsurvivors, survivors were younger, had a lower number of inotropes or vasopressors used before BiPella, and were more likely to have both devices implanted simultaneously during the same procedure. Compared with nonsurvivors, survivors had lower pulmonary artery pressures and RV stroke work index before BiPella. Indices of RV afterload were quantified for 14 subjects. Among these patients, nonsurvivors had higher pulmonary vascular resistance (6.8; 95% confidence interval [95% CI], 5.5-8.1 versus 1.9; 95% CI, 0.8-3.0; P<0.01), effective pulmonary artery elastance (1129; 95% CI, 876-1383 versus 458; 95% CI, 263-653; P<0.01), and lower pulmonary artery compliance (1.5; 95% CI, 0.9-2.1 versus 2.7; 95% CI, 1.8-3.6; P<0.05). CONCLUSIONS: This is the largest, retrospective analysis of BiPella for cardiogenic shock. BiPella is feasible, reduces cardiac filling pressures and improves cardiac output across a range of causes for cardiogenic shock. Simultaneous left ventricular and RV device implantation and lower RV afterload may be associated with better outcomes with BiPella. Future prospective studies of BiPella for cardiogenic shock are required.

Acute Hemodynamic Effects of Intra-aortic Balloon Counterpulsation Pumps in Advanced Heart Failure.

BACKGROUND: The utility of intra-aortic balloon counterpulsation pumps (IABPs) in low cardiac output states is unknown and no studies have explored the impact of IABP therapy on ventricular workload in patients with advanced heart failure (HF). For these reasons, we explored the acute hemodynamic effects of IABP therapy in patients with advanced HF. METHODS: We prospectively studied 10 consecutive patients with stage D HF referred for IABP placement before left ventricular assist device (LVAD) surgery and compared with 5 control patients with preserved left ventricular (LV) ejection fraction (EF) who did not receive IABP therapy. Hemodynamics were recorded using LV conductance and pulmonary artery catheters. Cardiac index (CI)-responder and CI-nonresponder status was assigned a priori as being "equal to or above" or below the median of the IABP effect on CI, respectively, within 24 hours after IABP activation. RESULTS: Compared with controls, patients with advanced HF had lower LVEF, lower LV end-systolic pressure, lower LV stroke work, and higher LV end-diastolic pressures and volumes before IABP activation. IABP activation reduced LV stroke work primarily by reducing end-systolic pressure. IABP therapy increased CI by a median of 20% as well as increased diastolic pressure time index and the myocardial oxygen supply:demand ratio. Compared with CI-nonresponders, CI-responders had higher systemic vascular resistance, lower right heart filling pressures, and a trend toward lower left heart filling pressures with improved indices of right heart function. Compared with CI-nonresponders, the diastolic pressure time index was increased among CI-responders. CONCLUSIONS: IABP therapy may be effective at reducing LV stroke work, increasing CI, and favorably altering the myocardial oxygen supply:demand ratio in patients with advanced HF, especially among patients with low right heart filling pressures and high systemic vascular resistance.